SARS-CoV-2 infection suppresses ACE2 function and antiviral immune response in the upper respiratory tract of infected patients
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Abstract
There is an urgent need to elucidate the molecular mechanisms underlying the transmissibility and pathogenesis of SARS-CoV-2. ACE2 is a host ectopeptidase with well-described anti-inflammatory and tissue protective functions and the receptor for the virus. Understanding SARS-CoV-2-ACE2 interaction and the expression of antiviral host genes in early infection phase is crucial for fighting the pandemic. We tested the significance of soluble ACE2 enzymatic activity longitudinally in positive nasopharyngeal swabs at two time points after symptom consultation, along with gene expression profiles of ACE2 , its proteases, ADAM17 and TMPRRS2 , and interferon-stimulated genes (ISGs), DDX58 , CXCL10 and IL-6 . Soluble ACE2 activity decreased during infection course, in parallel to ACE2 gene expression. On the contrary, SARS-CoV-2 infection induced expression of the ISG genes in positive SARS-CoV-2 samples at baseline compared to negative control subjects, although this increase wanes with time. These changes positively correlated with viral load. Our results demonstrate the existence of mechanisms by which SARS-CoV-2 suppress ACE2 expression and function casting doubt on the IFN-induced upregulation of the receptor. Moreover, we show that initial intracellular viral sensing and subsequent ISG induction is also rapidly downregulated. Overall, our results offer new insights into ACE2 dynamics and inflammatory response in the human upper respiratory tract that may contribute to understand the early antiviral host response to SARS-CoV-2 infection.
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SciScore for 10.1101/2020.11.18.388850: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study protocol was approved by the institutional review board of Hospital Germans Trias i Pujol.
Consent: All participants provided written informed consent.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Similarly, a group of COVID-19 negative nasopharyngeal swabs (n=20) were collected following the same procedure and matched by age and sex to the infected patients (mean age: 39 years and 70% females). Table 2: Resources
Software and Algorithms Sentences Resources Statistical analysis was performed using STATA 15.1. STATAsuggested: (Stata, RRID:SCR_012763)Results from OddPub: We did not detect open data. …
SciScore for 10.1101/2020.11.18.388850: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study protocol was approved by the institutional review board of Hospital Germans Trias i Pujol.
Consent: All participants provided written informed consent.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Similarly, a group of COVID-19 negative nasopharyngeal swabs (n=20) were collected following the same procedure and matched by age and sex to the infected patients (mean age: 39 years and 70% females). Table 2: Resources
Software and Algorithms Sentences Resources Statistical analysis was performed using STATA 15.1. STATAsuggested: (Stata, RRID:SCR_012763)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04304053 Completed Treatment of COVID-19 Cases and Chemoprophylaxis of Contacts… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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